trabedersen (ot-101) with pembrolizumab for newly diagnosed advanced nsclc and positive pd-l1

Conditions: Non-small Cell Lung Cancer

Summary: the goal of this clinical trial is to: 1) evaluate the safety and recommended dose of the drug ot-101/trabedersen when combined with pembrolizumab and 2) determine the efficacy of the combination therapy in adults with certain types of non-small cell lung cancer. the main question(s) it aims to answer are: * what medical problems to participants have when taking ot101 together with pembrolizumab? * what is the correct dose of ot-101 to use when evaluating the safety and efficacy of the combination therapy? * does the combination therapy delay progression or relapse of the participant\&#39;s non-small cell lung cancer? participants will: * receive intravenous ot-101/trabedersen for 4 days once every 2 weeks. clinic visits are required to receive and disconnect the infusion. * receive intravenous pembrolizumab once every 6 weeks.

the goal of this clinical trial is to: 1) evaluate the safety and recommended dose of the drug ot-101/trabedersen when combined with pembrolizumab and 2) determine the efficacy of the combination therapy in adults with certain types of non-small cell lung cancer. the main question(s) it aims to answer are: * what medical problems to participants have when taking ot101 together with pembrolizumab? * what is the correct dose of ot-101 to use when evaluating the safety and efficacy of the combination therapy? * does the combination therapy delay progression or relapse of the participants non-small cell lung cancer? participants will: * receive intravenous ot-101/trabedersen for 4 days once every 2 weeks. clinic visits are required to receive and disconnect the infusion. * receive intravenous pembrolizumab once every 6 weeks. in phase i, dose escalation/de-escalation of ot101/trabedersen is performed using a boin design to determine dose limiting toxicity (dlt) and the recommended phase 2 dose (rp2d) when combined with pembrolizumab. in phase ii, subjects receive the rp2d of ot101/trabedersen together with pembrolizumab until disease relapse, progression \[as determined by immune response evaluation criteria in solid tumours (irecist) criteria\], or death.

Eligibility criteria:
inclusion criteria: * age ≥ 19 years * histologically/cytologically proven diagnosis of non-small cell lung cancer (nsclc) with a pd-l1 of at least 1% * metastatic disease or disease not amenable for curative intent therapy * no prior treatment for metastatic nsclc. early-stage disease therapy acceptable if completed at least six months prior and did not include immunotherapy. * eastern cooperative oncology group (ecog) performance status ≤ 2 * measurable disease by recist criteria * adequate organ and marrow function as defined below: * absolute neutrophil count ≥1,500/mm3 * platelets ≥100,000/mm3 * hemoglobin \>9.0 mg/dl * creatinine clearance \> 60 ml/min/1.73 m2 using chronic kidney disease epidemiology collaboration (ckd-epi) formula * total serum bilirubin \ 2.5 x uln * aspartate aminotransferase (ast)/serum glutamic-oxaloacetic transaminase (sgot) and alanine aminotransferase (alt)/serum glutamic-pyruvic transaminase (sgpt) ≤ 2.5 x uln; if participant has liver metastases, ≤5x uln * for females of childbearing potential, negative serum or urine pregnancy test ≤7 days of treatment, \& agree to use effective contraceptive during treatment \& 90 days after end of treatment * male participants must agree to use effective contraception during the trial \& for 90 days after end of treatment * able to give informed consent exclusion criteria: * received any systemic treatments including investigational agents within the last 28 days * known hypersensitivity to any of the excipients of ot101 or pembrolizumab * received radiotherapy within 14 days of the study intervention. palliative radiation is allowed during the study with a 1-week washout * pregnant or breast-feeding women * history of autoimmune diseases that required systemic treatment in the past 2 years with agents such as, but not limited to, corticosteroids or immunosuppressive drugs. thyroid replacement for hypothyroidism, insulin treatment for type i diabetes or corticosteroids adrenal/pituitary insufficiency are allowed. * uncontrolled systemic diseases that in the opinion of the investigator may interfere with the protocol activities * known active second malignancy that needs treatment. exceptions include basal cell or squamous cancers of the skin, bladder or cervical carcinoma in situ, prostate cancer on hormone therapy alone. * immunodeficiency diagnosis or receiving chronic steroids that exceed a dose equivalent to prednisone 10 mg daily * symptomatic brain metastases. asymptomatic metastases or having received treatment for brain metastases and are off steroid therapy is acceptable. * known psychiatric or substance use that would interfere with the study requirements * inability to co-operate with the requirements of the protocol

Keywords: newly diagnosed pd-l1